title: Functional implications of IgG anti-endothelial cell antibodies in pulmonary arterial hypertension.
abstract: The objective of this study was to research the functionality of anti-endothelial cell antibodies (AECA) in pulmonary arterial hypertension (PAH) by assessing the effects of IgG from AECA-positive PAH patients on the induction of adhesion molecules on human umbilical vein endothelial cells (HUVECs) and on the production of pro-inflammatory cytokines and chemokines by HUVECs. To achieve this purified IgG from 28 PAH patients were included. IgG from systemic sclerosis (SSc) (n = 58) and systemic lupus erythematosus (SLE) (n = 16) patients without PAH were included as disease controls. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression on HUVECs, incubated with patient IgG, were quantified by flow cytometry. Production of interleukin (IL)-1β, -6, -8, and CC chemokine ligand 2 (CCL2) by HUVECs, incubated with patient IgG, were quantified by multiplex flow cytometry. Our results showed that IgG from AECA-positive PAH, SSc and SLE patients induced significantly higher expression of ICAM-1, VCAM-1, and E-selectin and production of IL-6, -8, and CCL2 compared to IgG from AECA-negative patients and IgG from healthy controls. Like in SLE and SSc, IgG from AECA-positive PAH patients can activate endothelial cells to a pro-adhesive and pro-inflammatory state. Therefore, IgG AECA could play a pathogenic role by inducing inflammatory injury of vascular endothelium which is considered a key player in the initiation and progression of PAH.
authors.affiliation: Department of Internal Medicine/Division of Clinical & Experimental Immunology, CARIM, Maastricht University Medical Centre , Maastricht , the Netherlands .
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Arends
authors.forename: Jan G M C
authors.initials: JG
authors.lastname: Damoiseaux
authors.forename: Adriaan M
authors.initials: AM
authors.lastname: Duijvestijn
authors.forename: Lucienne
authors.initials: L
authors.lastname: Debrus-Palmans
authors.forename: Karin A
authors.initials: KA
authors.lastname: Boomars
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Cohen Tervaert
authors.forename: Pieter
authors.initials: P
authors.lastname: van Paassen
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology; D015331:Cohort Studies; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D065627:Familial Primary Pulmonary Hypertension; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045743:Scleroderma, Diffuse / Q000276:immunology / Q000473:pathology; D012595:Scleroderma, Systemic / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G